NIPD – NIPT – fetal genetics from maternal blood

Diagnostic tests such as amniocentesis or chorion villus sampling (CVS) are accurate for detecting fetal trisomies, but are invasive and pose a slight risk (0.5%) for procedure-related inadvertent fetal loss. Therefore noninvasive screening tests have been developed in recent years which aim at most accurately characterising those pregnancies which are truly at risk for fetal disease before a diagnostic invasive test be done on reasonable grounds: Once tested positive (conspicuous) the logic consequence of this measure is to undergo an invasive, confirmatory testing. On the other hand, this approach serves to avoid risk-prone procedeures among the vast majority of fetuses who in fact carry a truly low residual risk for fetal disease. Therefore, the primary purpose of non invasive testing is to protect healthy fetuses from unneccessary invasive procedures on the basis of rational reasons.

Well-established screening tests in this field (stand-alone serum blood tests and tests combined with ultrasound, e.g. NT scan) are also noninvasive, but lack from a false positive rate of up to 5%, equaling a test specificity of 95%. (Such tests may report a pregnancy as positive for a fetal Trisomy when it is in fact negative—false positive). They miss 5 – 10% of fetal Trisomy 21 cases, equaling a test sensitivity of 90-95%.

In order to markedly reduce these shortcomings, a new generation of noninvasive screening tests has recently been developed: They are based on a novel principle of collecting and analysing fetal DNA, which is circulating in maternal blood. Thus, a direct noninvasive access to specific, individual fetal gene information has become possible.To distinguish these new tests from the aforementioned established test strategies this principle (Detecting cell free DNA fragments from both the mother and fetus in the mother’s blood circulation to determine if there is an increased quantity of a particular chromosome as would be seen in a trisomy pregnancy) was coined "Non-invasive prenatal testing or screening (NIPT)".

NIPT in its current state of development solely aims at detecting common fetal trisomies (trisomy 21—Down syndrome, trisomy 18 and Trisomy 13) during the first and second trimesters. Due to their nature, these tests completely omit any structural information about the fetus in the assessment of fetal health. Therefore, any of these tests must be complemented by an early, structured ultrasound analysis of the fetus carried out by an experienced ultrasound examiner. In contrast to invasive diagnostic testing (CVS and amniocentesis), NIPT does not pose a risk of miscarraiage to the pregnancy since it involves only a maternal blood sample. There are several laboratory tests on the market, which are based on the same principle but who have different procedural characteristics (molecular genetic target region, analysis algorithm) yielding different test performance data and slightly different indications for clinical application (see below).

Non-invasive prenatal screening can be ordered by healthcare professionals for women with pregnancies of at least 11 weeks gestational age and should always be carried out by a prenatal specialist in conjuction with an early anomaly ultrasound scan.

Please note: The testing is available for all patients when requested, but may not be covered by health insurance.

All patients having non-invasive prenatal testing need to meet with a genetically certified prenatal counselor to understand the scope and limitations of this testing.

Detection rates for Trisomy 21 (Down syndrome) are greater than 98.6% with a false positive rate of less than 0.2%. Detection rates for trisomy 18 (Edward syndrome) are 97.2-99.9% and for trisomy 13 (Patau syndrome) are 78.6-91.7%.

Low Risk result: With a Low Risk result , the chance of having a baby with Trisomy 21, Trisomy 18, or Trisomy 13 is low. In rare instances, the test will not detect these birth defects as it cannot detect all affected pregnancies.

High Risk result: If testing indicates a High Risk, there is an increased chance of having a baby with Trisomy 21, Trisomy 18, or Trisomy 13. If your result is High Risk, your healthcare provider may offer genetic counseling and diagnostic testing to determine if you baby is affected with one of these conditions.